Association between oxidative DNA damage and telomere shortening in circulating endothelial progenitor cells obtained from metabolic syndrome patients with coronary artery disease.

Metabolic syndrome (MS) induces an increase in oxidative stress and may be an important contributory factor for coronary artery disease (CAD). Telomere shortening of endothelial progenitor cells (EPCs) may be the key factor in endothelial cell senescence. The rate of telomere shortening is highly dependent on cellular oxidative damage. This study analyzed the relationship between telomere shortening and oxidative DNA damage in EPCs obtained from CAD patients with MS and without MS. We analyzed circulating EPCs in peripheral blood obtained from 57 patients with CAD (acute myocardial infarction [AMI], n=26; stable angina pectoris [AP], n=31) and 21 age-matched healthy subjects (control). Telomere length and telomerase activity were significantly lower in CAD patients than in controls, and were lower in AMI patients than in AP patients. Oxidative DNA damage was higher in CAD patients compared with controls, and oxidative DNA damage in AMI patients was also higher than in AP patients. There was a negative correlation between telomere length and oxidative DNA damage. Telomere length and telomerase activity were lower in CAD patients with MS than in those without MS. Oxidative DNA damage in CAD patients with MS was higher than in those without MS. In our in vitro study, oxidative treatments induced telomere shortening and decrease in telomerase activity of EPCs. These results suggest that EPC telomere shortening via increased oxidative DNA damage may play an important role in the pathogenesis of CAD. In addition, MS may be related to increased oxidative DNA damage and EPC telomere shortening.